title: Intravenous transplantation of mesenchymal stem cells preconditioned with early phase stroke serum: current evidence and study protocol for a randomized trial.
abstract: BACKGROUND
  Recovery after a major stroke is usually limited, but cell therapy for patients with fixed neurologic deficits is emerging. Several recent clinical trials have investigated mesenchymal stem cell (MSC) therapy for patients with ischemic stroke. We previously reported the results of a controlled trial on the application of autologous MSCs in patients with ischemic stroke with a long-term follow-up of up to 5 years (the 'STem cell Application Researches and Trials In NeuroloGy' (STARTING) study). The results from this pilot trial are challenging, but also raise important issues. In addition, there have been recent efforts to improve the safety and efficacy of MSC therapy for stroke.
  
  
  METHODS
  The clinical and preclinical background and the STARTING-2 study protocol are provided. The trial is a prospective, randomized, open-label, blinded-endpoint (PROBE) clinical trial. Both acute and chronic stroke patients will be selected based on clinical and radiological features and followed for 3 months after MSC treatment. The subjects will be randomized into one of two groups: (A) a MSC group (n = 40) or (B) a control group (n = 20). Autologous MSCs will be intravenously administered after ex vivo culture expansion with autologous ischemic serum obtained as early as possible, to enhance the therapeutic efficacy (ischemic preconditioning). Objective outcome measurements will be performed using multimodal MRI and detailed functional assessments by blinded observers.
  
  
  CONCLUSIONS
  This trial is the first to evaluate the efficacy of MSCs in patients with ischemic stroke. The results may provide better evidence for the effectiveness of MSC therapy in patients with ischemic stroke.
  
  
  BACKGROUND
  This trial was registered with ClinicalTrials.gov, number NCT01716481.
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, 135-710, Gangnam-gu, Seoul, South Korea. nmboy@unitel.co.kr.
authors.forename: Suk Jae
authors.initials: SJ
authors.lastname: Kim
authors.forename: Gyeong Joon
authors.initials: GJ
authors.lastname: Moon
authors.forename: Won Hyuk
authors.initials: WH
authors.lastname: Chang
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Oh Young
authors.initials: OY
authors.lastname: Bang
mesh_terms: D000208:Acute Disease; D002478:Cells, Cultured; D002908:Chronic Disease; D002985:Clinical Protocols; D006801:Humans; D007262:Infusions, Intravenous; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D011446:Prospective Studies; D020127:Recovery of Function; D012107:Research Design; D044967:Serum / Q000378:metabolism*; D020521:Stroke / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome